Inhibition of ornithine decarboxylase by the isomers of 1,4-dimethylputrescine.

N Moyano, J Frydman, G Buldain, O Ruiz, R B Frydman

Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Argentina.

Journal of medicinal chemistry 1990 Jul

filter terms:

1,4-Dimethylputrescine (2,5-hexanediamine) was separated into its racemic and meso isomers by fractional crystallization of its dibenzoyl derivative. The racemic form was resolved into its (+)- and (-)-isomers with (+)- and (-)-dibenzoyltartaric acids. None of the three isomers (meso, +, and -) inhibited ornithine decarboxylase (ODC) activity in vitro, while all the three were strongly inhibitory of ODC when assayed in vivo in rats or in H-35 hepatoma cells. In rat liver the three isomers also decreased the putrescine pool while only the (+)-isomer decreased spermidine content. In the H-35 cells the (-)- and (+)-isomers decreased the spermidine and spermine content. When ODC was induced in the latter by insulin it was found that the (-)-isomer strongly inhibited protein and ODC synthesis, while the (+)-isomer and the meso isomer were less inhibitory. The meso isomer was a good inducer of ODC antizyme in rat liver, while the (+)- and (-)-isomers were poor inducers of the former.

Citation

N Moyano, J Frydman, G Buldain, O Ruiz, R B Frydman. Inhibition of ornithine decarboxylase by the isomers of 1,4-dimethylputrescine. Journal of medicinal chemistry. 1990 Jul;33(7):1969-74